B-HRT Introduction

As the life expectancy of women increases, the number of years a woman will experience the sometimes debilitating effects of menopause will similarly increase. This has focused more attention on the primary treatment for menopause and it’s perceived risks and potential benefits. This focus has resulted in a large number of trials being conducted over the past decade.

There is a significant amount of supporting clinical evidence for the findings below. Studies have produced some consistent findings that have resulted in widely accepted protocols for treatment. However, the studies have also produced several conflicting findings that have generated debate within the medical profession and caused concerns to patients.

Unopposed estrogen therapy increases the risk of endometrial cancer in women with an intact uterus

Use of estrogen combined with progesterone eliminates the risk of endometrial cancer

The combination of estrogen and progesterone in the right ratio reduces or eliminates the occurrence of irregular blood loss which otherwise could result in the need for a hysterectomy

Hormone Replacement Therapy has a positive influence on overall bone growth, hence a beneficial effect in reducing the risk of osteoporosis

Several studies indicate that HRT produces benefits in the prevention of cardiac conditions. Support for this view is not universal. The indications are that HRT does in fact have a beneficial effect on factors that influence cardiac health (e.g. cholesterol). The argument from some quarters is that these effects would not necessarily translate directly into a measurement for the prevention of cardiac events. The effect HRT has on risk factors to heart problems can however be viewed as an important secondary benefit.

The use of HRT comes with some level of increased risk. These conflicting results both positive and negative (many of the studies, were carried out by well renowned and well-respected research groups) give rise to the current uncertainties and patient concerns. It is not clear whether the conflicting results stem from trends or from unreliabilities in the structure of the studies.

There are two long-term studies which have received much attention. The British study (Women International Study of long Duration Estrogen use after Menopause) was due to be published in 2011, but terminated after 1 year due to increased cardiovascular and thromboembolic risk (in women with cardiovascular risk factors) when started many years after menopause. However, the mean age of women who had been recruited at the time the study was stopped was 62.8 years.

The other, a U.S. study conducted by the Women Health Initiative (WHI) completed in 2006 again recruited women with an average age of 63 years. It showed increased coronary events, strokes, breast cancer and pulmonary embolism and decreased osteoporotic fractures and colon cancer. Subsequent analysis of the data has shown that the timing of initiation of therapy is critical in relation to the risks of HRT.

A large French study of 54,000 women (Fournier et al, “Breast Cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort” Int J Cancer 2005 Apr 10;114(3):448-54) compared the use of estrogen/synthetic progestins to the use of estrogen/micronised progesterone. The relative risks of breast cancer were 1.4 and 0.9 respectively, indicating that bio-identical micronised progesterone is preferable to synthetic progestins in short-term HRT (mean duration of use 2.8 years). This was evident whether the estrogen was oral or transdermal/percutaneous.

At this point it is important to consider the differences in action between synthetic progestin and bio-identical progesterone. The two are clearly not interchangeable. In the area of breast cancer we need to take a cautious and balanced approach by considering the family and personal history of the patient. If for example family history indicates a high risk of osteoporosis and a low risk of breast cancer, then the benefits of HRT would appear to outweigh the risks. In addition the gains in terms of relief from menopause symptoms would outweigh the minimal risk associated with the short-term use of HRT.

Hormones Used

The hormones commonly used in this treatment regime are generally restricted to

Estrogens are commonly as Triest which is a combination of estrone (E1) 10%, estradiol (E2) 10% and estriol (E3) 80%

Progesterone

Dehydroepiandrosterone (DHEA)

Testosterone.

Although individual hormones may be compounded, it is common practice to prescribe a combination of hormones in the one troche. More information about these hormones is provided in the attached data sheets.

Natural Hormones

The vast majority of HRT users worldwide are prescribed synthetic hormones. A small but increasing number are opting for natural or bio-identical hormones, usually because these have been found to be more patient friendly or an alternative when the commercially available medications have caused unavoidable adverse reactions. The word “natural” is somewhat of a misnomer. We prefer another commonly used term “bio-dentical”, as a more accurate way to represent these hormones. The connection probably relates to the source of the diosogen being the wild Mexican yam plant; although in reality the hormones are still produced by chemical synthesis.

Dr Marker discovered the route for manufacture of bio-identical hormones in the 1940’s. He devised a synthesis route for converting the sapogin diosgenin, into progesterone. The subsequently named Marker Degradation was later modified to produce testosterone, cortisone and estrogen. The importance of these products is not in the source but in their chemical structure. The bio-identical hormones share the identical chemical structure to the body’s internally manufactured hormones.

Unlike synthetic hormones, there have not been a huge amount of trials conducted on bio-identical hormones. The main reason is financial, as bio-identical hormones are not based on invented synthetic structures they cannot be patented. This means they are of little interest to the major drug companies who understandably will not fund expensive clinical studies on material where they are not able to achieve exclusivity for any product they manufacture. One interesting study by Hagrove et al was published in Obstet. Gynecol. in 1989. This study indicated the use of bio-identical hormones produced far less side effects than the use of synthetics. These findings are supported in practice by the number of women who successfully use bio-identical hormones after ceasing synthetic HRT due to adverse reactions.

BIO – identical HRT

Bio-Identical HRTThere are three major differences when using bio-identical HRT, compared to the use of synthetics:

The structure of the hormones

The dosage form of the treatment

The philosophy of prescribing it is a combination of these three factors, which results in the effectiveness of the treatment.

The dominant dosage form for bio-identical hormones is the troche or trans-buccal (sub-lingual) delivery. Trans-dermal is used to a lesser extent (it has been found to be less effective than trans-buccal due to the patient to patient variability in absorption rates through the skin). In either case, the advantage of avoiding oral administration is bypassing the high first-pass metabolism of the hormones in the liver. Patients using the trans-buccal route insert a small, slow dissolving troche (lozenge) between gum and cheek. The formula is designed so that the troche dissolves in the cheek cavity within 30 minutes. The troche is flavored to mask the bitter taste of the hormones. Peak hormone levels are achieved after ~one hour of administering the troche and levels revert to baseline after approximately six to seven hours depending on the hormone. This route is particularly effective in consistently delivering physiologically effective concentrations of the hormones into the blood stream. A clinical study on the pharmocokinetics of this route of administering hormones to menopausal women has been completed by Stenlake Compounding Chemist (Wren B. G. et al, ” Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women” Climacteric 2003;6:104-111).

The third unique part of the bio-identical HRT process is the philosophy of prescribing. This is carried out on a case-by-case basis where the dosage regime is designed around the individual patient baseline blood plasma levels, their current symptoms and response to the initial hormone treatment. This is only feasible because the troches are formulated and compounded for the individual patient. As we compound the medication we are able to produce a wide combination of dosages and hormone ratios. This is clearly not possible using fixed dose synthetic hormones.

This combination of:

bio-identical hormones which are not foreign to the human body

the effective trans-buccal administration route

the ‘customized’ dosage

Results in a treatment that is successful where use of synthetic HRT has failed or a patient chooses not to use for other reasons.